• Title/Summary/Keyword: Carcinogenicity

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Effect of GE-132 on the Hepatic Bromobenzene Metabolizing Enzyme System in Rats (유기게르마늄(GE-132)이 Bromobenzene의 대사계에 미치는 영향)

  • 김석환;조태현;최종원
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.6
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    • pp.702-708
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    • 1993
  • The study was attempted to elucidate the mechanism of GE-132(100mg/kg, p.o. for 6 weeks) on the metabolism of bromobenzene (460mg/kg, i.p. bid, for 2 days), which has potent carcinogenicity, mutagenicity and hepatotoxicity. It showed that activities of cytochrome p-450, aminopyrine demethylase and aniline hydroxylase, which have epoxide generating property, were not changed by GE-132 treatment. On the other hand, epoxide hydrolase was not changed but that glutathione S-transferase was significantly increased by GE-132 treatment. And also ${\gamma}-glutamylcysteine$ synthetase was not changed following the GE-132 treatment, but the activity of glutathione reductase was significantly increased. The level of hepatic glutathione which was decreased by bromobenzene recovered markedly by GE-132 pretreatment. It is concluded that the mechanism for the observed effect of GE-132 on bromobenzene metabolism is due to the induction of glutathione S-transferase.

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Differential Display Analysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Identified Induction of Ras-related Nuclear Protein Binding Protein2 (RanBP2) Gene

  • Kim, Dong-Hak;Lim, Young-Ran;Park, Hyoung-Goo;Kim, Beom-Joon;Chun, Young-Jin
    • Toxicological Research
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    • v.25 no.1
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    • pp.35-40
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    • 2009
  • TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related halogenated aromatic hydrocarbons elicit a diverse spectrum of biochemical and toxic responses in laboratory animals and mammalian cells in culture. Toxicity and carcinogenicity of TCDD is well established but the molecular mechanism is still poorly understood. Here, we found the noble responsive genes to TCDD using the differential display analysis. Treatment of HepG2 cells with TCDD showed a significantly different mRNA expression pattern from the untreated cells in differential display analysis. The differentially displayed bands were isolated and used as probes in dot blot and Northern blot analyses. Of thirty-five isolated differentially displayed bands, only two bands were confirmed as positive in dot blot and Northern blot analyses. The nucleotides sequences of these clones were analyzed and the search of Genebank database revealed that one clone is highly homologous with RanBP2 (Ras-related nuclear protein binding protein2; 92%) and the other is an unknown gene. RanBP2 is a nucleoporin with SUMO E3 ligase activity that functions in both nucleocytoplasmic transport and mitosis and its role as a novel tumor suppressor has been recently proposed. Thus, these results may suggest the clue elucidating the toxic mechanism of TCDD through RanBP2.

The Cancer-Preventive Potential of Panax ginseng - A Review of Human and Experimental Evidence - (인삼(Panax ginseng) 항암 효과에 관한 문헌고찰 - 실험연구와 역학연구 결과를 중심으로 -)

  • Kim, Joon-Youn;Lee, Duk-Hee;Yun, Taik-Koo;Morgan, Gareth;Vainio, Harri;Shin, Hai-Rim
    • Journal of Preventive Medicine and Public Health
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    • v.33 no.4
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    • pp.383-392
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    • 2000
  • Objective : We have reviewed the potential cancer preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in oriental countries. Data identification and study selection: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-2000) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were also considered. Results : Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. Conclusion : While Panax ginseng C. A. Meyer has shown cancer preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

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Protective effect of dietary chitosan on cadmium accumulation in rats

  • Kim, Mi Young;Shon, Woo-Jeong;Park, Mi-Na;Lee, Yeon-Sook;Shin, Dong-Mi
    • Nutrition Research and Practice
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    • v.10 no.1
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    • pp.19-25
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    • 2016
  • BACKGROUND/OBJECTIVES: Cadmium is a toxic metal that is an occupational and environmental concern especially because of its human carcinogenicity; it induces serious adverse effects in various organs and tissues. Even low levels of exposure to cadmium could be harmful owing to its extremely long half-life in the body. Cadmium intoxication may be prevented by the consumption of dietary components that potentially reduce its accumulation in the body. Dietary chitosan is a polysaccharide derived from animal sources; it has been known for its ability to bind to divalent cations including cadmium, in addition to other beneficial effects including hypocholesterolemic and anticancer effects. Therefore, we aimed to investigate the role of dietary chitosan in reducing cadmium accumulation using an in vivo system. MATERIALS/METHODS: Cadmium was administered orally at 2 mg (three times per week) to three groups of Sprague-Dawley rats: control, low-dose, and high-dose (0, 3, and 5%, respectively) chitosan diet groups for eight weeks. Cadmium accumulation, as well as tissue functional and histological changes, was determined. RESULTS: Compared to the control group, rats fed the chitosan diet showed significantly lower levels of cadmium in blood and tissues including the kidneys, liver, and femur. Biochemical analysis of liver function including the determination of aspartate aminotransferase and total bilirubin levels showed that dietary chitosan reduced hepatic tissue damage caused by cadmium intoxication and prevented the associated bone disorder. CONCLUSIONS: These results suggest that dietary chitosan has the potential to reduce cadmium accumulation in the body as well as protect liver function and bone health against cadmium intoxication.

Lack of the Initiation of Benzo[a]pyrene-induced Mouse Forestomach Neoplasia by Di(2-ethylhexyl)phthalate(DEHP)

  • Lee, Sang-Ho;Le, Young-Chun;Kim, Jeong-Ok;Ha, Yeong-Lae
    • Preventive Nutrition and Food Science
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    • v.2 no.2
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    • pp.96-100
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    • 1997
  • Carcinogenicity of di(2-ethylhexyl)phthalate(DEHP) to the mose forestomach and its inhibitor activity for the initiation of Benzo[a]pyrene(BP)-induced mouse forestomach neoplasia were studied on the mouse forestomach carcinogenesis regimen. One hundred female ICR mice(6~7 weeks of age) were hosed in a poly-carbonate cage (4 mice/cage) in a humidity- and temperature-controlled room subjected to a semipurified diet for a week. Mice were divided into 4 treatment groups (25 mice/treatment): Basal diet, DEHP, BP, and BP+DEHP. On Monday and wednesday, 0.1ML DEHP mixed with 0.1ml olive oil (for DEHP and DEHP+BP treatment groups) or 0.1ml saline+0.1ml olive oil (for basal diet group) was intubated, p.o., and on Friday, 2mg BP dissolved in 0.2ml olive oil (for BP and BP+DEHP treatment groups) was intubated, p.o. This cycle was repeated for 4 weeks. Beginning with the first intubation of BP an continuing thereafter, body weight and food intake were recorded once and twice weekly, respectively. All surviving mice were sacrificed 22 weeks after the first dose of BP intubation and countered forestomach tumor. No tumor was formed by DEHP treatment. 5.75 tumors per mouse was formed by BP treatment, whereas its number was reduced to 4.53 by BP+DEHP treatment. Similar results were seen in the tumor incidence. Body weight gain was not affected by DEHP treatment, when compared to that b basal diet treatment. The body weight was significantly reduced by BP treatment, but its reduction was recovered to the level of the basal diet group by BP+DEHP treatment. No significant difference was seen in food intake among all treatment groups. These results indicate that DEHP lacks carcinogenic activity to the mose forestomach and rather inhibits the initiation of BP-induced mose forestomach neoplasia.

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Risk Assessment of Drometrizole, a Cosmetic Ingredient used as an Ultraviolet Light Absorber

  • Lee, Jae Kwon;Kim, Kyu-Bong;Lee, Jung Dae;Shin, Chan Young;Kwack, Seung Jun;Lee, Byung-Mu;Lee, Joo Young
    • Toxicological Research
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    • v.35 no.2
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    • pp.119-129
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    • 2019
  • As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

Concentration and risk assessment of indoor air quality in day care centers and postnatal care centers (보육시설, 산후조리원의 실내공기질 농도 및 위해성평가)

  • An, Jihee;Oh, Yujin;Im, Ji Young;Ahn, Mun Seob;Hong, Eunju;Son, Bu-Soon
    • Journal of odor and indoor environment
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    • v.17 no.4
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    • pp.337-345
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    • 2018
  • In this study, we measured the concentration of Particulate Matter($PM_{10}$), Formaldehyde(HCHO), and Total Bacteria Count (TBC) at two facilities: day care centers, and postnatal care centers located in the cities of Gyeonggi, Gangwon, Jeolla and Gyeongsang from January 1, 2012 to December 31, 2015. $PM_{10}$ concentration was similar to the day care centers and postnatal care centers. HCHO concentration was the highest in the postnatal care centers. TBC concentration was the highest in the day care centers. Comparing the different cities, $PM_{10}$ concentration was the highest in Gyeonggi, HCHO concentration was the highest in Gyeonggi, and TBC concentration was the highest in Gyeonggi. As a result of HCHO's risk assessment, it was found that adults exceeded the carcinogenicity tolerance of $10^{-6}$ specified by the US EPA. This study is expected to be helpful in preventing damage to health from the contaminated indoor air at sensitive facilities, and can be used as basic data for indoor air quality management.

Hazard Levels of Cooking Fumes in Republic of Korea Schools

  • Lee, Iu-Jin;Lee, Sang-Gil;Choi, Bo-Hwa;Seo, Hoe-Kyeong;Choi, Ji-Hyung
    • Safety and Health at Work
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    • v.13 no.2
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    • pp.227-234
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    • 2022
  • Background and Purpose: In 2021, lung cancer in school food workers was first recognized as an occupational cancer. The classification of the carcinogenicity of cooking fumes by International Agency for Research on Cancer (IARC) was based on Chinese epidemiological data. This study aimed to determine the hazard levels of school cooking fumes in Korea. Materials and Methods: Based on public school cafeterias in one area, 25 locations were selected for the survey according to the number per school type, ventilation states, and environmental pre-assessments of cafeterias. Two inside cooking areas using a heat source and one outside cooking area were selected as control measurement points. Measurements of CO, CO2, polycyclic aromatic hydrocarbons (PAHs), and total volatile organic compounds (TVOCs), including benzene, formaldehyde, and particulate matter (PM10, PM2.5, PM1, respectively), were taken. The concentrations and patterns of each substance in the kitchens were compared with the outdoor air quality. Result: Known carcinogens, such as the concentrations of PAHs, formaldehyde, TVOC (benzene), and particulate matter in school cooking fumes, were all detected at similar or slightly higher levels than those found outside. Additionally, substances were detected at relatively low concentrations compared to the Chinese cooking fumes reported in the literature. However, the short-term exposure to high concentrations of CO (or composite exposure with CO2) and PM2.5 in this study were shown. Conclusion: The school cooking fumes in South Korea was a relatively less harmful than Chinese cooking fumes, however short-term, high exposure of toxic substances can cause a critical health effect.

A Study on the Selection of Candidates for Substances Subject to Permission Using Chemicals Ranking and Scoring (CRS) (화학물질 우선순위 선정기법(CRS)을 활용한 허가대상 후보물질 선정 연구)

  • Kim, Hyo-dong;Park, Kyo-shik
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.32 no.3
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    • pp.253-267
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    • 2022
  • Objectives: This study was performed to check whether the CRS (Chemical Ranking and Scoring) system is appropriate as a method to determine substances as candidates for substances subject to permission and to apply this system to the selection of candidates for substances subject to permission. Methods: A risk score was obtained by multiplying the hazard score and the exposure score and then ranking them. The hazard sub-indicators are carcinogenicity, germ cell mutagenicity, reproductive toxicity, specific target organ toxicity-repeated exposure, respiratory sensitization and endocrine disrupting chemicals. Exposure sub-indicators are persistence, bioaccumulation and emission volume. Sensitivity analysis was performed for missing values. Correlation analysis and multivariable linear regression analysis were performed among hazard, exposure and risk in order to confirm that CRS was an appropriate method. Results: As a result of the sensitivity analysis on missing values, it was confirmed that the effect on the risk ranking was not sensitive. Correlation and regression analysis confirmed that exposure had a greater effect on risk than hazard. Conclusions: The CRS system, which derives a risk score using a hazard and exposure score, is judged to be appropriate as a method for the selection of preliminary of candidates for substances subject to permission. Benzene, cadmium, nickel, and cobalt were selected as priority candidates for substances subject to permission.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity

  • Mei-qing Qiu;Hui-jun Wang;Ya-fei Ju;Li Sun;Zhen Liu;Tao Wang;Shi-feng Kan;Zhen Yang;Ya-yun Cui;You-qiang Ke;Hong-min He;Shu Zhang
    • Journal of Gastric Cancer
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    • v.23 no.2
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    • pp.340-354
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    • 2023
  • Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.